ArticleProceedings of the National Academy of Sciences of the United States of America2002
A basolateral sorting motif in the MICA cytoplasmic tail.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 124 citations in OpenAlex.
- Article
- Sequence and structural insights of monoleucine-based sorting motifs contained within the cytoplasmic domains of basolateral proteins.Frontiers in cell and developmental biology · 2024Review
- CLPTM1L is a GPI-anchoring pathway component targeted by HCMV.The Journal of cell biology · 2023Article
- Major Histocompatibility Complex Class I Chain-Related α (MICA) STR Polymorphisms in COVID-19 Patients.International journal of molecular sciences · 2022Article
- Immunogenetics of Lupus Erythematosus.Advances in experimental medicine and biology · 2022Article
- Role of Polymorphisms of NKG2D Receptor and Its Ligands in Acute Myeloid Leukemia and Human Stem Cell Transplantation.Frontiers in immunology · 2021Review
- Article
- MICA polymorphisms associated with antithyroid drug-induced agranulocytosis in the Chinese Han population.Immunity, inflammation and disease · 2020Article
- Distinct roles for luminal acidification in apical protein sorting and trafficking in zebrafish.The Journal of cell biology · 2020Article
- Impact of MICA and NKG2D polymorphisms in HLA-fully matched related and unrelated hematopoietic stem cell transplantation.Bone marrow transplantation · 2018Article
- A new MHC-linked susceptibility locus for primary Sjögren's syndrome: MICA.Human molecular genetics · 2017Article
- How Mucosal Epithelia Deal with Stress: Role of NKG2D/NKG2D Ligands during Inflammation.Frontiers in immunology · 2017Review
- Cryptic protein-protein interaction motifs in the cytoplasmic domain of MHCI proteins.BMC immunology · 2016Article
- MICA*A4 protects against ulcerative colitis, whereas MICA*A5.1 is associated with abscess formation and age of onset.Clinical and experimental immunology · 2016Article
- A Distinctive Cytoplasmic Tail Contributes to Low Surface Expression and Intracellular Retention of the Patr-AL MHC Class I Molecule.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- Immunogenetic biomarkers in inflammatory bowel diseases: role of the IBD3 region.World journal of gastroenterology · 2014Review
- N-glycosylation of asparagine 8 regulates surface expression of major histocompatibility complex class I chain-related protein A (MICA) alleles dependent on threonine 24.The Journal of biological chemistry · 2014Article
- A cis-eQTL of HLA-DRB1 and a frameshift mutation of MICA contribute to the pattern of association of HLA alleles with cervical cancer.Cancer medicine · 2014Article
- A variant upstream of HLA-DRB1 and multiple variants in MICA influence susceptibility to cervical cancer in a Swedish population.Cancer medicine · 2014Article
- MICA variant promotes allosensitization after kidney transplantation.Journal of the American Society of Nephrology : JASN · 2013Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The MHC class I chain-related MICA molecule is a stress-induced, highly polymorphic, epithelia-specific, membrane-bound glycoprotein interacting with the activating NK cell receptor NKG2D and/or gut-enriched Vdelta1-bearing gammadelta T cells. We have previously reported the presence of a MICA transmembrane-encoded short-tandem repeat harboring a peculiar allele, A5.1, characterized by a frame shift mutation leading to a premature intradomain stop codon, thus denying the molecule of its 42-aa cytoplasmic tail. Given that this is the most common population-wide MICA allele found, we set out to analyze the functional consequences of cytoplasmic tail deletion. Here, we show native expression of MICA at the basolateral surface of human intestinal epithelium, the site of putative interaction with intraepithelial T and NK lymphocytes. We then demonstrate, in polarized epithelial cells, that although the full-length MICA protein is sorted to the basolateral membrane, the cytoplasmic tail-deleted construct as well as the naturally occurring A5.1 allele are aberrantly transported to the apical surface. Site-directed mutagenesis identified the cytoplasmic tail-encoded leucine-valine dihydrophobic tandem as the basolateral sorting signal. Hence, the physiological location of MICA within epithelial cells is governed by its cytoplasmic tail, implying impairment in A5.1 homozygous individuals, perhaps relevant to the immunological surveillance exerted by NK and T lymphocytes on epithelial malignancies.
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